Brack Kerstin, Berk Iris, Magulski Thomas, Lederer Jörg, Dotzauer Andreas, Vallbracht Angelika
Department of Virology, University of Bremen, D-28359 Bremen, Germany.
J Virol. 2002 Dec;76(23):11920-30. doi: 10.1128/jvi.76.23.11920-11930.2002.
The consequences of a hepatitis A virus (HAV) infection on cell-based antiviral responses and the interactions between virus and host cells resulting in persistent infections are poorly understood. In this report, we show that HAV does inhibit double-stranded (dsRNA)-induced beta interferon (IFN-beta) gene expression by influencing the IFN-beta enhanceosome, as well as dsRNA-induced apoptosis, which suggests that both effects may be connected by shared viral and/or cellular factors. This ability of HAV, which preserves the sites of virus production for a longer time, may allow the virus to establish an infection and may be the presupposition for setting up persistent infections. Our results suggest that the inhibitory effect of HAV on the cellular defense mechanisms might not be sufficient to completely prevent the antiviral reactions, which may be induced by accumulating viral dsRNA, at a later stage of infection. However, HAV seems to counteract this situation by downregulation of viral replication and in the following production of viral dsRNA. This ability of noncytopathogenic HAV acts dominantly on cytopathogenic HAV in trans. The downregulation might ensure the moderate replication which seems necessary for inhibition of the antiviral mechanisms by HAV and therefore for the persistent state of the HAV infection.
甲型肝炎病毒（HAV）感染对基于细胞的抗病毒反应的影响，以及导致持续性感染的病毒与宿主细胞之间的相互作用，目前尚不清楚。在本报告中，我们表明HAV确实通过影响IFN-β增强体以及dsRNA诱导的细胞凋亡来抑制双链（dsRNA）诱导的β干扰素（IFN-β）基因表达，这表明这两种效应可能由共同的病毒和/或细胞因子联系起来。HAV的这种能力能使病毒产生位点在更长时间内得以保留，可能有助于病毒建立感染，并且可能是建立持续性感染的前提条件。我们的结果表明，HAV对细胞防御机制的抑制作用可能不足以完全阻止抗病毒反应，在感染后期，这种反应可能由积累的病毒dsRNA诱导产生。然而，HAV似乎通过下调病毒复制以及随后病毒dsRNA的产生来应对这种情况。非细胞病变性HAV的这种能力可反式作用于细胞病变性HAV。这种下调可能确保适度的复制，这似乎是HAV抑制抗病毒机制以及因此维持HAV感染持续状态所必需的。
